Review article
ARE WE ENTERING CHEMO-FREE ERA IN CHRONIC LYMPHOCYTIC LEUKEMIA? THE ROLE OF IBRUTINIB AND VENETOCLAX AND LESSONS LEARNT FROM IDELALISIB
VIBOR MILUNOVIĆ
orcid.org/0000-0003-0069-6688
; Lombardi Comprehensive Cancer Centre, Georgetown University, United States of America; Merkur University Hospital, Department for Hematology, Zagreb, Croatia
INGA MANDAC ROGULJ
; Merkur University Hospital, Department for Hematology, Zagreb,
ANA PLANINC-PERAICA
; Merkur University Hospital, Department for Hematology; University of Zagreb, School of Medicine, Zagreb, Croatia
SLOBODANKA OSTOJIĆ KOLONIĆ
; Merkur University Hospital, Department for Hematology; University of Zagreb, School of Medicine, Zagreb, Croatia
Abstract
The main aim of this review is to present a novel class of agents, the inhibitors of B cell receptor (BCR) signaling pathway, used in the treatment of chronic lymphocytic leukemia (CLL) as the most common leukemia in the Western world. Traditionally, CLL was treated with immunochemotherapy, but certain subpupulations (elderly, biological prognostic factors) had poor outcome. With advances in our understanding the pathogenesis of intracellular pathways, the possibility of selective inhibition and targeted therapy in CLL has arisen. The fi rst agent in the class of BCR inhibitors, ibrutinib, a Bruton kinase inhibitor, has been shown superior in phase III clinical trials eliminating negative prognostic factors such as del(17p), with adequate toxicity profi le, which was recognized by the respective regulatory agencies. Other BCR inhibitors idelalisib and venetoclax are extremely active in relapsed setting, but unfortunately, idelalisib combinations in fi rst line clinical trials resulted in unacceptable toxicity, which is a cautionary tale on designing trials. Despite their effi cacy, we are only at the beginning to improve them by combination with monoclonal antibodies, immunochemotherapy, or between each other to improve outcomes of CLL treatment even further. However, the main obstacle to chemo-free era in CLL is their price resulting in limited access to these agents and inequity in the modern treatment of CLL.
Keywords
chronic lymphocytic leukemia; ibrutinib; idelalisib; venetoclax
Hrčak ID:
186102
URI
Publication date:
2.9.2017.
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